ArticleThe Journal of biological chemistry2013
Next generation sequencing in predicting gene function in podophyllotoxin biosynthesis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 121 citations in OpenAlex.
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- Cloning and bioinformatics analysis of key gene ShOMT3 of podophyllotoxin biosynthesis pathway in Sinopodophyllum hexandrum.PloS one · 2025Article
- Genomic characterization and identification of candidate genes for putative podophyllotoxin biosynthesis pathway in Penicillium herquei HGN12.1C.Microbial biotechnology · 2024Article
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- Structure-function analysis of CYP719As involved in methylenedioxy bridge-formation in the biosynthesis of benzylisoquinoline alkaloids and its de novo production.Microbial cell factories · 2023Article
- Transgenic Forsythia plants expressing sesame cytochrome P450 produce beneficial lignans.Scientific reports · 2022Article
- Production of beneficial lignans in heterologous host plants.Frontiers in plant science · 2022Article
- Synthesis of (-)-deoxypodophyllotoxin and (-)-epipodophyllotoxin via a multi-enzyme cascade in E. coli.Microbial cell factories · 2021Article
- Physiological and Transcriptomic Analysis Provide Insight into Low Temperature Enhancing Hypericin Biosynthesis inMolecules (Basel, Switzerland) · 2021Article
- Dirigent Proteins Guide Asymmetric Heterocoupling for the Synthesis of Complex Natural Product Analogues.Journal of the American Chemical Society · 2021Article
- Lignans of Sesame (Molecules (Basel, Switzerland) · 2021Review
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- Recent Advances in the Synthetic Biology of Natural Drugs.Frontiers in bioengineering and biotechnology · 2021Review
- Uncovering the cytochrome P450-catalyzed methylenedioxy bridge formation in streptovaricins biosynthesis.Nature communications · 2020Article
- Over 100 Million Years of Enzyme Evolution Underpinning the Production of Morphine in the Papaveraceae Family of Flowering Plants.Plant communications · 2020Article
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- Comparative Transcriptomics Analysis for Gene Mining and Identification of a Cinnamyl Alcohol Dehydrogenase Involved in Methyleugenol Biosynthesis fromMolecules (Basel, Switzerland) · 2018Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Podophyllum species are sources of (-)-podophyllotoxin, an aryltetralin lignan used for semi-synthesis of various powerful and extensively employed cancer-treating drugs. Its biosynthetic pathway, however, remains largely unknown, with the last unequivocally demonstrated intermediate being (-)-matairesinol. Herein, massively parallel sequencing of Podophyllum hexandrum and Podophyllum peltatum transcriptomes and subsequent bioinformatics analyses of the corresponding assemblies were carried out. Validation of the assembly process was first achieved through confirmation of assembled sequences with those of various genes previously established as involved in podophyllotoxin biosynthesis as well as other candidate biosynthetic pathway genes. This contribution describes characterization of two of the latter, namely the cytochrome P450s, CYP719A23 from P. hexandrum and CYP719A24 from P. peltatum. Both enzymes were capable of converting (-)-matairesinol into (-)-pluviatolide by catalyzing methylenedioxy bridge formation and did not act on other possible substrates tested. Interestingly, the enzymes described herein were highly similar to methylenedioxy bridge-forming enzymes from alkaloid biosynthesis, whereas candidates more similar to lignan biosynthetic enzymes were catalytically inactive with the substrates employed. This overall strategy has thus enabled facile further identification of enzymes putatively involved in (-)-podophyllotoxin biosynthesis and underscores the deductive power of next generation sequencing and bioinformatics to probe and deduce medicinal plant biosynthetic pathways.
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